Akinfenwa scored his third and fourth goals of the campaign, his first since August, to earn the visitors a victory that sees them climb four places in the League One table.
Tranmere's Ryan Lowe headed just wide in an opening 45 minutes that offered little in terms of goalscoring chances, but ended with Gillingham snatching a half-time lead.
Two minutes into stoppage time at the end of the first period, Akinfenwa collected a loose ball on the left edge of the box before drilling a shot into the bottom right corner.
The Merseyside outfit were dealt another blow 12 minutes after the break when Jim McNulty was sent off for bringing down Cody McDonald, who missed two great chances at the beginning of the half, when the Gills striker was running through on goal.
McDonald continued to be involved heavily when his header was cleared off the line two minutes later, but Gillingham were not to be denied a two-goal cushion as Akinfenwa pounced to tap in a rebound on 69 minutes after his initial effort came back off the post.
Lowe pulled one back for Rovers on 77 minutes when a long ball over the top split open the Gills defence and allowed the experienced striker to tuck the ball under visiting keeper Stuart Nelson, who had decided not to come off his line.
However, being a man down, Tranmere struggled to mount any late pressure on Peter Taylor's side, who comfortably held out for a win that sees them climb to 13th in the table, seven places above the hosts.